Features of the course of primary and recurrent herpetic keratitis developing following COVID-19 vaccination
DOI:
https://doi.org/10.31288/oftalmolzh2025138Keywords:
COVID-19, herpetic keratitis, recurrent herpetic keratitis, herpes virus, cornea, vaccineAbstract
Purpose: To assess the features of the course of primary and recurrent herpetic keratitis (HK) developing following COVID-19 vaccination.
Material and Methods: Medical records of 31 patients (34 eyes) with post-COVID-19 vaccination HK were reviewed. The patients were divided into two post-COVID-19 vaccination HK groups: group 1 with primary HK (9 patients; 9 eyes) and group 2 with recurrent HK (22 patients; 25 eyes). Levels of total vitamin D, and immunoglobulin G (IgG) antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD), herpes simplex virus (HSV)-1/2, cytomegalovirus (CMV) and Epstein-Barr nuclear antigen (EBNA) were assessed in venous serum.
Results: The median time (interquartile range (IQR)) from COVID-19 vaccination to the development of keratitis was 15 days (10-30) for patients with primary HK and 7 days (4-10) for patients with recurrent HK. The level of vitamin D in venous serum was lower than normal in 84.2% of the total sample of patients. Of the eyes that developed primary HK following COVID-19 vaccination, 3 (33.3%) had dendritic HK and 6 (66.7%) had non-necrotizing stromal HK. Of the eyes that developed recurrent HK following COVID-19 vaccination, 2 (8%) had dendritic HK, 21 (81%) had non-necrotizing stromal HK and 2 (6%) had ulcerative necrotizing HK.
Conclusion: Non-necrotizing stromal HK was the most common form of post COVID-19 vaccination HK in both groups. The level of vitamin D in venous serum was lower than normal in 84.2% of post COVID-19 vaccination patients with HK. Levels of anti-HSV IgG, anti-EBNA IgG, anti-VZV IgG, and anti-CMV IgG antibodies in venous serum exceeded normal ranges in 86.5%, 96.4%, 92%, and 88.8%, respectively, of post COVID-19 vaccination patients with HK.
References
Harris RJ, Hall JA, Zaidi A, Andrews NJ, Dunbar JK, Dabrera G. Effect of Vaccination on Household Transmission of SARS-CoV-2 in England. N Engl J Med. 2021 Aug 19;385(8):759-60. https://doi.org/10.1056/NEJMc2107717
Skowronski DM, se Serres G. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2021;384:1576-1577. https://doi.org/10.1056/NEJMc2036242
Tanriover MD, Doganay HL, Akova M, Guner HR, Azap A, Akhan S, et al.; CoronaVac Study group. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): Interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021 Jul 17;398(10296):213-222. https://doi.org/10.1016/S0140-6736(21)01429-X
Wang MT, Niederer RL, McGhee CN, Danesh-Meyer HV. COVID-19 Vaccination and the Eye. Am J Ophthalmol. 2022;240:79-98. https://doi.org/10.1016/j.ajo.2022.02.011
Haseeb AA, Solyman O, Abushanab MM, Obaia ASA, Elhusseiny AM. Ocular Complications Following Vaccination for COVID-19: A One-Year Retrospective. Vaccines. 2022;10:342. https://doi.org/10.3390/vaccines10020342
Lee Y-K, Huang Y-H. Ocular Manifestations after Receiving COVID-19 Vaccine: A Systematic Review. Vaccines (Basel). 2021 Nov 27;9(12):1404. https://doi.org/10.3390/vaccines9121404
ElSheikh RH, Haseeb A, Eleiwa TK, Elhusseiny AM. Acute Uveitis following COVID-19 Vaccination. Ocul Immunol Inflamm. 2021 Aug 18;29(6):1207-1209. https://doi.org/10.1080/09273948.2021.1962917
Pichi F, Aljneibi S, Neri P, Hay S, Dackiw C, Ghazi NG. Association of Ocular Adverse Events with Inactivated COVID-19 Vaccination in Patients in Abu Dhabi. JAMA Ophthalmol. 2021 Oct 1;139(10):1131-1135. https://doi.org/10.1001/jamaophthalmol.2021.3477
Jampol LM, Tauscher R, Schwarz HP. COVID-19, COVID-19 Vaccinations, and Subsequent Abnormalities in the Retina: Causation or Coincidence? JAMA Ophthalmol. 2021 Oct 1;139(10):1135-1136. https://doi.org/10.1001/jamaophthalmol.2021.3483
Phylactou M, Li JO, Larkin DFP. Characteristics of endothelial corneal transplant rejection following immunisation with SARS-CoV-2 messenger RNA vaccine. Br J Ophthalmol. 2021 Jul;105(7):893-896. https://doi.org/10.1136/bjophthalmol-2021-319338
Wasser LM, Roditi E, Zadok D, Berkowitz L, Weill Y. Keratoplasty Rejection After the BNT162b2 messenger RNA Vaccine. Cornea. 2021 Aug 1;40(8):1070-1072. https://doi.org/10.1097/ICO.0000000000002761
Li S, Jia X, Yu F, Wang Q, Zhang T, Yuan J. Herpetic Keratitis Preceded by COVID-19 Vaccination. Vaccines (Basel). 2021 Nov 25;9(12):1394. https://doi.org/10.3390/vaccines9121394
Richardson-May J, Rothwell A, Rashid M. Reactivation of herpes simplex keratitis following vaccination for COVID-19. BMJ Case Rep. BMJ Case Rep. 2021 Sep 7;14(9):e245792. https://doi.org/10.1136/bcr-2021-245792
WHO. Safety Surveillance Manual second edition. Geneva: World Health Organization; 2021. Covid-19 vaccines.
Barker NH. Ocular herpes simplex. BMJ Clin Evid. 2008;2008:0707.
Naumann G, Gass JD, Font RL. Histopathology of herpes zoster ophthalmicus. Am J Ophthalmol. 1968;65:533-541. https://doi.org/10.1016/0002-9394(68)93869-5
Liesegang TJ. Classification of Herpes Simplex Virus Keratitis and Anterior Uveitis. Cornea. 1999 Mar;18(2):127-43. https://doi.org/10.1097/00003226-199903000-00001
Grillo AP, Fraunfelder FW. Keratitis in association with herpes zoster and varicella vaccines. Drugs Today (Barc). 2017 Jul;53(7):393-397. https://doi.org/10.1358/dot.2017.53.7.2667582
Rothova A, de Groot JD, Mudrikova T. Reactivation of acute retinal necrosis after flu H1N1 vaccination. Br J Ophthalmol. 2011, 95, 291. https://doi.org/10.1136/bjo.2010.185983
Rand KH, Rasmussen LE, Pollard RB, Arvin A, Merigan TC. Cellular immunity and herpes virus infections in cardiac transplant patients. N Engl J Med. 1977 Jun 16;296(24):1372-7. https://doi.org/10.1056/NEJM197706162962402
Cheng JY, Margo CE. Ocular adverse events following vaccination: Overview and update. Surv Ophthalmol. 2022 Mar-Apr;67(2):293-306. https://doi.org/10.1016/j.survophthal.2021.04.001
Walter R, Hartmann K, Fleisch F, Reinhart WH, Kuhn M. Reactivation of herpes virus infections after vaccinations? Lancet. 1999;353:810. https://doi.org/10.1016/S0140-6736(99)00623-6
Hassman LM, Di Loreto DA Jr. Immunologic factors may play a role in herpes simplex virus 1 reactivation in the brain and retina after influenza vaccination. ID Cases. 2016 Sep 22:6:47-51. https://doi.org/10.1016/j.idcr.2016.09.012
McMahon DE, Amerson E, Rosenbach M, et al. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases. J Am Acad Dermatol. 2021 Jul;85(1):46-55. https://doi.org/10.1016/j.jaad.2021.03.092
Song MY, Koh KM, Hwang KY, et al. Relapsed disciform stromal herpetic keratitis following mRNA COVID-19 vaccination: a case report. Korean J Ophthalmol. 2022 Feb;36(1):80-82. https://doi.org/10.3341/kjo.2021.0150
Alkwikbi H, Alenazi M, Alanazi W, Alruwaili S. Herpetic Keratitis and Corneal Endothelitis Following COVID-19 Vaccination: A Case Series. Cureus. 2022 Jan 5;14(1):e2096 https://doi.org/10.7759/cureus.20967
Papasavvas I, de Courten C, Herbort CP. Varicella-zoster virus reactivation causing herpes zoster ophthalmicus (HZO) after SARS-CoV-2 vaccination - report of three cases. J Ophthalmic Inflam Infect. 2021 Sep 16;11(1):28. https://doi.org/10.1186/s12348-021-00260-4
Fard AM, Desilets J, Patel S. Recurrence of Herpetic Keratitis after COVID-19 Vaccination: A Report of Two Cases. Case Rep Ophthalmol Med. 2022 May 19:2022:7094893. https://doi.org/10.1155/2022/7094893
Sridharan M, Navitskas DS, Kock ME, Houghton ED, Heikal MN, Chen D, et al. Evaluation of soluble fibrin monomer complex in patients in SARS-CoV-2 COVID-19 infection-associated coagulopathy. Eur J Haematol. 2022 Apr;108(4):319-326. Epub 2022 Jan 10. https://doi.org/10.1111/ejh.13738
Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, et al. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev. 2019 Aug 1;40(4):1109-1151. https://doi.org/10.1210/er.2018-00126
Domazet Bugarin J, Dosenovic S, Ilic D, Delic N, Saric I, Ugrina I, et al. Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients-Randomized Controlled Trial. Nutrients. 2023 Feb 28;15(5):1234. https://doi.org/10.3390/nu15051234
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